Cystic FibrosisPhase 3NCT03125395
A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
A Phase 3 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 20 sites in 2 countries.
Trial summary
A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- LUM/IVA
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 12 May 2017to 17 Jul 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Subjects entering the Treatment Cohort must meet the following criteria:
- Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132)
- Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit
- Subjects entering the Observational Cohort must meet 1 of the following criteria:
- Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort.
- Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort.
- Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required.
Who cannot join
- Prematurely discontinued LUM/IVA treatment in Study 115B.
- History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering LUM/IVA to the subject
- History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor.
- Subjects with a history of allergy or hypersensitivity to LUM/IVA.
- Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified.
- QTc value at the completion of Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor
- History of poor compliance with LUM/IVA and/or procedures in Study 115B as deemed by the investigator.
- Participation in an investigational drug trial (including studies investigating LUM and/or IVA) other than Study 115B.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
United States17 sites
Children's Hospital Colorado
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
The Lung & Cystic Fibrosis Center at Women's & Children's Hospital of Buffalo
Buffalo, New York, 14222
University of North Carolina Hospitals
Chapel Hill, North Carolina, 27514
Medical University of South Carolina
Charleston, South Carolina, 29425
Ann & Robert Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
University Hospitals Cleveland Medical Center/Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Texas Children's Hospital
Houston, Texas, 77030
Riley Hospital for Children at Indiana University Health
Indianapolis, Indiana, 46202
Children's Mercy Hospital
Kansas City, Missouri, 64108
Children's Respiratory and Critical Care Specialists, P.A., Children's Hospitals and Clinics of Minn
Minneapolis, Minnesota, 55404
Children's Hospital of the King's Daughters
Norfolk, Virginia, 23507
Stanford University
Palo Alto, California, 94305
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Seattle Children's Hospital
Seattle, Washington, 98105
Canada3 sites
McGill University Health Centre, Glen Site, Montreal Children's Hospital
Montreal, Quebec, H4A 3J1
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia's Children's Hospital
Vancouver, British Columbia, V6H 3N1
About this study
Official title: A Phase 3, Rollover Study to Evaluate the Safety of Long-term Treatment With Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.
- Conditions
- Cystic Fibrosis
- Being tested
- LUM/IVA
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LUM/IVADrug
Also called VX-809/VX-770, lumacaftor/ivacaftor
Participants received LUM/IVA every q12h.
| Study group | Role | What they receive |
|---|---|---|
| LUM/IVA | Experimental | LUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age. Receives: Drug: LUM/IVA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: Day 1 up to Week 98
Secondary outcomes (15)
Absolute Change in Sweat Chloride
Sweat samples were collected using an approved collection device.
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in Body Mass Index (BMI)
BMI was defined as weight in kilogram (kg) divided by height in square meter (m^2).
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in BMI-for-age Z-score
BMI was defined as weight in kilograms divided by height in m^2. z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in Weight
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in Weight-for-age Z-score
Z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change From Baseline in Stature (Height)
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in Stature-for-age Z-score
Z-score is a statistical measure to describe whether a mean was above or below the standard. A z-score of 0 is equal to the mean and is considered normal. Lower numbers indicate values lower than the mean and higher numbers indicate values higher than the mean.
Measured: From Parent Study 115B Baseline at Week 96
Time-to-first Pulmonary Exacerbation
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.
Measured: From Parent Study 115B Baseline through Week 96
Number of Pulmonary Exacerbations (PEx)
Pulmonary exacerbation was defined as new or changed treatment with oral, inhaled, or intravenous antibiotics and fulfillment of pre-specified protocol-defined criteria.
Measured: From Parent Study 115B Baseline through Week 96
Number of Cystic Fibrosis (CF) Related Hospitalizations
Measured: From Parent Study 115B Baseline through Week 96
Absolute Change in Fecal Elastase-1 (FE-1) Levels
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels
Measured: From Parent Study 115B Baseline at Week 96
Number of Participants With Microbiology Culture Status (Positive or Negative)
Following microbial tests were performed: Burkholderia, Methicillin Resistant Staphylococcus Aureus (MRSA), Methicillin Susceptible Staphylococcus Aureus (MSSA), Pseudomonas Aeruginosa Mucoid (P. Aeruginosa Mucoid), P. Aeruginosa Non-Mucoid, P. Aeruginosa Small Colony Variant and Stenotrophomonas Maltophilia.
Measured: Week 96
Absolute Change in Lung Clearance Index (LCI) 2.5
LCI 2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value.
Measured: From Parent Study 115B Baseline at Week 96
Absolute Change in Lung Clearance Index (LCI) 5.0
LCI 5.0 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/20th of its starting value.
Measured: From Parent Study 115B Baseline at Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2017
- Study start12 May 2017
- Primary completion17 Jul 2019
- Study completion17 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by Vertex Pharmaceuticals IncorporatedThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vertex Pharmaceuticals Incorporated
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03125395
- Sponsor's protocol ID
- VX16-809-116
- Other IDs
- 2019-003112-31, 2019
- Status last verified
- Jul 2020
- First submitted
- 19 Apr 2017
- Last updated
- 7 Aug 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hoppe JE, Chilvers M, Ratjen F, McNamara JJ, Owen CA, Tian S, Zahigian R, Cornell AG, McColley SA. Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study. Lancet Respir Med. 2021 Sep;9(9):977-988. doi: 10.1016/S2213-2600(21)00069-2. Epub 2021 May 6.
PubMed 33965000
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Rollover Study to Evaluate the Safety of Long-term Treatment With Lumacaftor/Ivacaftor Combination Therapy in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation
- ClinicalTrials.gov ID
- NCT03125395
- Acronym / sponsor ID
- VX16-809-116
- Conditions
- Cystic Fibrosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Vertex Pharmaceuticals IncorporatedIndustry (pharma, biotech, devices)
- Study start
- 12 May 2017 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 17 Jul 2019 (actual)
- First posted
- 24 Apr 2017 (actual)
- Results
- Posted 7 Aug 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Rollover Safety Study of Lumacaftor/Ivacaftor in Subjects Aged 2 Years and Older With Cystic Fibrosis, Homozygous for F508del.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| LUM/IVA | Experimental | Drug: LUM/IVALUM/IVA granules or tablets were administered orally every 12 hours (Participants aged 2 through 5 years received LUM 100 mg/IVA 125 mg granules or LUM 150 mg/IVA 188 mg granules based on body weight. Participants ≥6 years of age were to receive LUM 200 mg/IVA 250 mg tablets). Doses were adjusted upward for changes in weight and age. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study VX15-809-115 Part B (Study 115B, NCT02797132)
- Willing to remain on a stable CF medication regimen through the Safety Follow-up Visit
- Completed 24 weeks of LUM/IVA treatment and the Safety Follow-up Visit in Study 115B, but do not want to enroll in the Treatment Cohort.
- Received at least 4 weeks of LUM/IVA treatment and completed visits up to Week 24 and the Safety Follow-up Visit, if required, of Study 115B but are not taking LUM/IVA at the end of the Study 115B Treatment Period (i.e., Week 24) because of a drug interruption and either did not receive Vertex approval to enroll in the Treatment Cohort or do not want to enroll in the Treatment Cohort.
- Permanently discontinued LUM/IVA in Study 115B after receiving at least 4 weeks of treatment and remained in the study from the time of treatment discontinuation through the Week 24 Visit and Safety Follow-up Visit, if required.
Key exclusion criteria (8 listed)
- Prematurely discontinued LUM/IVA treatment in Study 115B.
- History of any comorbidity or laboratory abnormality that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering LUM/IVA to the subject
- History of drug intolerance or other serious reactions to LUM/IVA in Study 115B that would pose an additional risk to the subject in the opinion of investigator, and which should be discussed with the Vertex medical monitor.
- Subjects with a history of allergy or hypersensitivity to LUM/IVA.
- Liver function test (LFT) abnormality meeting criteria for LUM/IVA treatment interruption at the completion of Study 115B, for which no convincing alternative etiology is identified.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LUM/IVAAlso: VX-809/VX-770, lumacaftor/ivacaftorParticipants received LUM/IVA every q12h. | Drug | LUM/IVA |
Primary outcome
Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Day 1 up to Week 98
15 secondary outcomes
Absolute Change in Sweat Chloride
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in Body Mass Index (BMI)
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in BMI-for-age Z-score
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in Weight
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in Weight-for-age Z-score
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change From Baseline in Stature (Height)
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in Stature-for-age Z-score
Time frame: From Parent Study 115B Baseline at Week 96
Time-to-first Pulmonary Exacerbation
Time frame: From Parent Study 115B Baseline through Week 96
Number of Pulmonary Exacerbations (PEx)
Time frame: From Parent Study 115B Baseline through Week 96
Number of Cystic Fibrosis (CF) Related Hospitalizations
Time frame: From Parent Study 115B Baseline through Week 96
Absolute Change in Fecal Elastase-1 (FE-1) Levels
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in Immunoreactive Trypsinogen (IRT) Serum Levels
Time frame: From Parent Study 115B Baseline at Week 96
Number of Participants With Microbiology Culture Status (Positive or Negative)
Time frame: Week 96
Absolute Change in Lung Clearance Index (LCI) 2.5
Time frame: From Parent Study 115B Baseline at Week 96
Absolute Change in Lung Clearance Index (LCI) 5.0
Time frame: From Parent Study 115B Baseline at Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33965000Hoppe JE, Chilvers M, Ratjen F, McNamara JJ, Owen CA, Tian S, Zahigian R, Cornell AG, McColley SA. Long-term safety of lumacaftor-ivacaftor in children aged 2-5 years with cystic fibrosis homozygous for the F508del-CFTR mutation: a multicentre, phase 3, open-label, extension study. Lancet Respir Med. 2021 Sep;9(9):977-988. doi: 10.1016/S2213-2600(21)00069-2. Epub 2021 May 6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LUM/IVA in people with Cystic Fibrosis, run by Vertex Pharmaceuticals Incorporated at 20 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) (time frame: Day 1 up to Week 98). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03125395, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2020.